Phosphoproteomics Reveals the Role of Constitutive KAP1 Phosphorylation by B-Cell Receptor Signaling in Chronic Lymphocytic Leukemia - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35533307/
Application of B-cell receptor (BCR) pathway inhibitor ibrutinib for chronic lymphocytic leukemia (CLL) is a major breakthrough, yet the downstream effects following inhibition of BCR signaling and during relapse await...
Conclusion: This phosphoproteomic analysis and functional validation illuminated the phosphorylation of KAP1 at S473 as an important downstream BCR signaling event and a potential indicator for the success of ibrutinib treatment in CLL.
Modeling the B-cell receptor signaling on single cell level reveals a stable network circuit topology between non-malignant B cells and chronic lymphocytic leukemia cells and between untreated cells and cells treated with kinase inhibitors - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35527719/
B-cell receptor (BCR) signaling is central for the pathomechanism of chronic lymphocytic leukemia (CLL), and inhibitors of BCR signaling have substantially improved treatment options. To model malignant and non-malignant BCR...
Conclusion/Relevance: To additionally test for the impact of therapeutic compounds on the network topology, we challenged the BCR signaling cascade with inhibitors for BTK (ibrutinib), PI3K (idelalisib), LYN (dasatinib), and SYK (entospletinib). Idelalisib treatment resulted in similar effects in malignant and non-malignant cells, whereas...
Multiple cells of origin in common with various types of mouse N-Myc acute leukemia
Source : https://www.sciencedirect.com/science/article/abs/pii/S0145212622000698?via=ihub
N-Myc overexpression induces B-ALL, T-ALL, AML, AUL, and MPAL in mice. * The multiple cells of origin are shared by different acute leukemia types. * The similar phenotypes are shared...
Conclusion/Relevance: Whole-genome sequencing revealed that retroviral integration sites were irrelevant to the leukemia types and that T-ALL and AML of MPAL shared the same integration site and many gene mutations, suggesting their common origin. Additionally, leukemic stem cells were identified in the KSL cell population, suggesting that the...
Inhibition of BTK and PI3Kδ impairs the development of human JMML stem and progenitor cells - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35443935/
1 Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: [email protected]. 2 Department of Pediatrics, Herman B Wells Center...
Conclusion/Relevance: RNAseq analysis of drug treated mice showed a profound reduction in the expression of genes associated with leukemic cell migration and inflammation, leading to correction in the infiltration of leukemic cells in the lung, liver and spleen. Remarkably, in a patient derived xenograft model of JMML, leukemia initiating stem...
Treatment paradigm in Waldenström macroglobulinemia: frontline therapy and beyond
Source : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9058343/
Saurabh Zanwar, Conceptualization, Data curation, Resources, Writing original draft, Writing review editing and Jithma P. Abeykoon, Conceptualization, Data curation, Methodology, Writing original draft, Writing review editing Waldenström macroglobulinemia (WM) is...
Conclusion: In the absence of head-to-head comparison between chemoimmunotherapy and Bruton’s tyrosine kinase inhibitors in otherwise fit patients with a MYD88L265P mutation, our preference is fixed duration therapy with four to six cycles of chemoimmunotherapy with bendamustine–rituximab. In this review, we discuss the role of MYD88 and...